Living with DNA Breaks is an Everyday Reality for Cells Adapted to High NaCl
Living with DNA Breaks is an Everyday Reality for Cells Adapted to High NaCl
复制标题
对于适应高氯化钠的细胞来说，DNA 断裂是每天的现实
作者：
N. Dmitrieva;M. Burg
对DNA断裂的快速、协调的反应，包括细胞周期检查点的激活和准确DNA修复的启动，被认为是维持基因组完整性和防止突变积累所必需的。这就是为什么最近出人意料地发现，在小鼠肾内髓质中，原本健康的细胞含有许多DNA断裂，但它们仍然存活并充分发挥功能。肾内髓质中的DNA断裂是由于尿浓缩机制导致细胞持续暴露于高NaCl浓度而引起的。在细胞培养中适应高NaCl的细胞也含有许多DNA断裂。DNA断裂不会触发细胞周期停滞或引起细胞凋亡，尽管它们存在，细胞仍安全地快速增殖。此外，高NaCl抑制经典DNA损伤反应的关键组分如Mre 11、chk 1和H2 AX的活性。为了解释为什么DNA断裂不会导致失能突变、致癌转化和/或凋亡，我们推测在高NaCl存在下，可能存在替代的DNA损伤反应途径或应对DNA损伤的特殊方式。
A rapid, coordinated response to DNA breaks, including activation of cell cycle checkpoints and initiation of accurate DNA repair is believed to be necessary to maintain genomic integrity and prevent accumulation of mutations. That is why it was so unexpected to discover recently that in the mouse renal inner medulla the otherwise healthy cells contain numerous DNA breaks, yet they survive and function adequately. The DNA breaks in the renal inner medulla are caused by the high NaCl concentrations to which the cells are constantly exposed as a consequence of the urinary concentrating mechanism. Cells adapted to high NaCl in cell culture also contain many DNA breaks. The DNA breaks do not trigger cell cycle arrest or cause apoptosis, and the cells safely proliferate rapidly despite their presence. Further, high NaCl inhibits the activity of key components of the classical DNA damage response such as Mre11, chk1 and H2AX. In order to explain why the DNA breaks do not cause disabling mutations, oncogenic transformations and/or apoptosis we speculate that in the presence of high NaCl there might be alternative DNA damage response pathways or special ways of coping with DNA damage.
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慢性高渗透压介导分子伴侣的组成型表达和对损伤的抵抗力。
DOI：
10.1152/ajprenal.00058.2002
发表时间：
2003
期刊：
American journal of physiology. Renal physiology
影响因子：
--
作者：
Santos,BentoC;Pullman,JamesM;Chevaile,Alejandro;Welch,WilliamJ;Gullans,StevenR
通讯作者：
Gullans,StevenR
DOI：
10.1073/pnas.0308463100
发表时间：
2004-02-24
影响因子：
11.1
作者：
Dmitrieva, NI;Cai, Q;Burg, MB
通讯作者：
Burg, MB
DOI：
10.1152/ajprenal.2000.278.2.f209
发表时间：
2000-02-01
影响因子：
4.2
作者：
Michea, L;Ferguson, DR;Burg, MB
通讯作者：
Burg, MB
DOI：
10.1016/s0928-4680(01)00074-8
发表时间：
2001-12-01
期刊：
Pathophysiology : the official journal of the International Society for Pathophysiology
影响因子：
--
作者：
Mongin, Alexander A.;Orlov, Sergei N.
通讯作者：
Orlov, Sergei N.
DOI：
10.1152/ajprenal.2001.280.5.f768
发表时间：
2001-05-01
影响因子：
4.2
作者：
Capasso, JM;Rivard, CJ;Berl, T
通讯作者：
Berl, T